Identification of residues in the V domain of CD80 (B7-1) implicated in functional interactions with CD28 and CTLA4.
Identification of residues in the V domain of CD80 (B7-1) implicated in functional interactions with CD28 and CTLA4.
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与CD28和CTLA4相互作用的CD80（B7-1）V结构域中残基的鉴定。
DOI：
10.1084/jem.182.3.667
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发表时间：
1995-09-01
期刊：
影响因子：
--
通讯作者：
Sékaly RP
中科院分区：
文献类型：
--
作者：
Fargeas CA;Truneh A;Reddy M;Hurle M;Sweet R;Sékaly RP
CD80 （B7-1）分子是免疫球蛋白超家族的45-60-kD成员，在多种造血来源的细胞类型上表达。CD80可以通过与T细胞表面分子CD28相互作用，为T细胞提供关键的共刺激信号。CD80还与CD28相关的分子CTLA4结合，CTLA4在活化的T细胞上表达。最近，CD28和CTLA4的其他配体已经在小鼠和人类中被描述。其中CD86 （B-70或B7-2）在分子水平上进行了表征。虽然预测的结构与CD80相似，但在氨基酸序列上却是远亲。在这项研究中，我们生成了人CD80突变体，并测试了它们维持与CD28相互作用的能力，从而导致粘附和增强IL-2的产生。CD80的V-like结构域中的两个疏水残基被鉴定为与CD28结合的关键，并且对与CTLA4的相互作用也很重要。这些残基邻近抑制CD28-CD80相互作用的BB1抗体的表位。其中一个残基Y87在从不同物种克隆的所有CD80和CD86中都是保守的。这些结果揭示了与CD28和CTLA4结合的结构要求。
The CD80 (B7-1) molecule is a 45-60-kD member of the immunoglobulin superfamily that is expressed on a variety of cell types of haematopoietic origin. CD80 can provide a critical costimulatory signal to T cells by interacting with the T cell surface molecule CD28. CD80 also binds to the CD28-related molecule CTLA4, which is expressed on activated T cells, Recently, additional ligands of CD28 and CTLA4 have been described in mice and humans. One of them, CD86 (B-70 or B7-2) was characterized at the molecular level. Although similar in predicted structure to CD80, it is distantly related in amino acid sequence. In this study, human CD80 mutants were generated and tested for their ability to maintain the interaction with CD28 leading to adhesion and enhanced IL-2 production. Two hydrophobic residues in the V-like domain of CD80 were identified as critical for binding to CD28 and are also important for the interaction with CTLA4. These residues are adjacent to the epitope of the BB1 antibody, which inhibits CD28-CD80 interactions. One of these residues, Y87, is conserved in all CD80 and CD86 cloned from various species. These results being to unravel the structural requirements for binding to CD28 and CTLA4.